How Fecal Transplants Work

Introduction to How Fecal Transplants Work

Unless you're a detective, a thief or a strangely nosy person, you wouldn't take your neighbor's trash and dump it in your kitchen, let alone consume it. On the other hand, if you were dying of scurvy, those limes they threw away after last night's margarita party might look surprisingly appetizing.

Accepting a transplant of someone else's stool, however carefully tested, might sound just as extreme, but -- thanks in part to its effectiveness in treating the intractable bug Clostridium difficile -- fecal microbiota transplantation might just be the next big thing in medicine [sources: Grady; Hudson; Mayo Clinic].

C. difficile, an emerging epidemic in hospitals and nursing homes, primarily affects older patients during long stays in care facilities. Like opportunistic weeds, the bacteria move into areas of the gut decimated by the very antibiotics intended to oust infections (antibiotics don't distinguish bacterial friend from foe). Once in the gut, C. difficile cranks out toxins that damage the intestinal lining, causing symptoms ranging from diarrhea to life-threatening colon inflammation. To make matters worse, C. difficile has grown increasingly virulent and antibiotic-resistant in recent years [sources: Grady; Hudson; Mayo Clinic].

Sending bacteria to fight bacteria makes good sense. Far from being a mere batch of bugs, many bacteria and other microbes are not only our friends, they are part of us. Our bodies contain nine to 10 times as many microbial cells as human ones; we each play host to 100 trillion bacteria. It's all part of a microbiome, an ecosystem of microbial communities that perform all kinds of useful work, from enabling digestion to aiding our immune systems [sources: Khoruts; Zimmer; Zimmer].

The recognition of microbial contributions to health has given rise to the growing field of medical ecology, which approaches the body's microbiome as a garden to be nurtured and, if necessary, weeded. Fecal transplantation extends this philosophy to "organically mulching" the gut garden: Stool from a healthy donor contains beneficial gut microorganisms, aka flora, 60-80 percent of which will take up residence in the recipient's gut, replacing those destroyed by antibiotics and infections, and overthrowing harmful communities like C. difficile [sources: Borody; Hudson].

Driving the need for such novel techniques are the ever-increasing numbers of people, particularly the elderly, who die each year from gastrointestinal infections. In the U.S. such deaths more than doubled from 1999 to 2007, rising from 7,000 to more than 17,000 a year [source: CDC]. Eighty-three percent of those fatalities occurred among patients over 65, two-thirds of whom died from C. difficile infections [source: CDC].

Fecal microbiota transplantation might sound outlandish or even a bit disgusting, but it restocks the body with some of the many microbes it needs to recover, live and thrive.

The Hygiene Hypothesis

Numerous studies suggest links between certain disorders and a lack of exposure to particular microbes. Children raised on farms, for example, develop fewer autoimmune disorders than urban children [source: Zimmer].

Along similar lines, people with asthma possess a different set of microbes than nonasthmatics. Reduced microbe exposure rates in the developed world could explain the recent uptick in occurrences of asthma and atopy -- a genetic predisposition toward developing allergic reactions [sources: Olszak et al.; Reibman et al.; Zimmer].

Bacteria: Flush With Success

Bacteria are arguably the most successful life-forms on Earth. You can find them clustered around deep-sea vents, buried far underground or teeming throughout larger organisms, including us. Our mouths alone contain hundreds to thousands of species, divided into colonial neighborhoods across our teeth, gums and tongue. Our lungs, once thought microbe-free, house 2,000 per square centimeter, and our guts could host as many as 25,000-30,000 different species [sources: Grady; Zimmer].

While we might think of them as microscopic menaces -- the sources of such delights as bacterial meningitis, urinary tract infections and food poisoning -- without bacteria, life as we know it would not exist. Starting 2.7-2.8 billion years ago, cyanobacteria released the first oxygen into the atmosphere; today, bacteria convert atmospheric nitrogen into something plants can use and recycle nutrients from dead organisms into the ecosystem [sources: Biello; Ingham; Farquhar, Bao and Thiemens].

Bacteria and other microbiota perform similar functions in our bodies. Gut microbes produce vitamins and reduce tough plant compounds into digestible slurry [source: Zimmer]. Within the immune system, bacteria help maintain skin's protective qualities, and nasal microbes produce an antibiotic shield against airborne germs. Moreover, microbes keep the immune system in check by limiting harmful swelling. It isn't a stretch to see how they might therefore play a role in inflammation-associated disorders, such as obesity, cardiovascular disease, type 2 diabetes and inflammatory bowel disease (IBD) [sources: Gewirtz; Zimmer; Zimmer].

Microbes also make healthier babies. Breast milk packs 600 species of bacteria and provides sugars that feed a baby's developing gut bacteria [sources: Hunt et al.; Zimmer; Zivkovic et al.]. According to a June 2011 PLoS One study, a woman's vaginal microbiome changes drastically when she becomes pregnant. Among other effects, this new environment might prepare newborns to digest breast milk [sources: Aagaard et al.; Zimmer]. Some studies suggest children born via cesarean section might be more prone to skin infections from methicillin-resistant Staphylococcus aureus (MRSA), a staph germ that resists first-line antibiotics such as penicillin and amoxicillin. Such children could also face greater risk of developing allergies or asthma [sources: CDC; Zimmer].

Exposure to certain microorganisms trains a child's developing immune system [source: Zimmer]. It also probably provides a natural defense against inflammatory bowel disease (IBD), a chronic or recurring inflammation of the gastrointestinal tract caused by a haywire immune response [sources: Olszak et al.; Zimmer]. IBD, which includes ulcerative colitis and Crohn's disease, ranks among the five most widespread gastrointestinal diseases in the United States and racks up health care costs of $1.7 billion annually [source: CDC].

When the stakes are so high, particularly for patients with life-threatening intestinal maladies, doctors have started thinking outside the box -- and inside the colon.

Coprophagy

Feces consumption occurs throughout nature, from the dung beetle to the ringtail possum. Animals primarily nosh on stool for its nutrient content. Some eat the excrement of herbivores, whose inefficient digestive tracts leave nutrients behind, while others -- particularly non-ruminating herbivores -- eat their own droppings to give their bodies another pass at the buffet. Some young animals also gain valuable gut microbes by consuming their parent's feces [sources: BBC; Encyclopaedia Britannica; Hirakawa; Saylor]. Bon appetit!

Will It Blend?

Although something like it might have been practiced as far back as fourth-century China, modern fecal transplantation was pioneered in 1958 by Dr. Ben Eiseman at Denver General Hospital [sources: Allen; Brandt; Eiseman]. Fecal transplants saw only sporadic use for decades afterward, but began coming into their own around 2000 [sources: Allen; Brandt].

Here's how they work: After screening a donor for HIV, hepatitis and other disease-causing germs, the doctor dilutes a stool sample with saline or 4 percent milk, and then blends it into a milkshake-like slurry [sources: Allen; Bakken et al.; Floch; Silverman, Davis and Pillai]. The mixture is then fed into a patient's digestive tract via nasogastric or nasoduodenal tubes, through a colonoscope or via a retention enema [sources: Allen; Bakken; Hudson]. A nasogastric tube feeds matter through the nasal passage, down the throat and into the stomach; a nasoduodenal tube extends a bit farther.

The patient prepares for the procedure via the traditional take-no-prisoners, date-with-the-thunder-bucket ritual used by colonoscopy patients [sources: Allen; Stein]. Stool donations usually come from family members or spouses, but some facilities have tried unrelated, prescreened donors [source: Allen; Brandt].

If a fecal transplant sounds like a great DIY project, it isn't. First, stool is a level 2 biohazard; second, if you don't test fecal samples for communicable diseases, you could end up in a world of hurt; third, remind us to never drink frozen margaritas at your house [source: Bakken et al.; Floch; Silverman, Davis and Pillai].

As of October 2012, U.S. insurance does not cover fecal transplants, but some doctors believe billing codes for the procedure will exist by early 2013, with Medicare coverage following a similar schedule [sources: Allen; Brandt; Gewirtz]. Dr. Andrew Gewirtz of the Georgia State University Center for Inflammation, Immunity & Infection agrees.

"I would guess it might be insurable soon -- although it is possible that use of specific, defined bacterial cocktails may supplant it eventually," he says.

The procedure's legal status may pose a greater challenge. According to Dr. Lawrence Brandt of the Albert Einstein College of Medicine, the U.S. Food and Drug Administration (FDA) has declared feces for fecal microbiota transplants a drug, which makes transplants -- already a fringe therapy -- illegal until the FDA approves their use. While doctors are unlikely to do time for performing the procedure, its dodgy status could work against them should a malpractice suit arise [source: Brandt].

On the plus side, drug classification could move fecal transplants further into the mainstream. To become a widely accepted medical practice, the process must be subjected to large-scale clinical trials, but gaining funding for such trials from, say, the National Institutes of Health (NIH), hinges upon the FDA granting a substance "investigational status." Classification as a drug places feces in a category that the FDA recognizes for this purpose [sources: Brandt; Khoruts; McKenna].

Once they work the bugs out, bacteriotherapy and fecal transplantation could offer hope to a lot of sick people.

Human Biome Project

In June 2012, around 200 scientists published the results of the Human Microbiome Project (HMP), a landmark genetic survey of the trillions of microbes composing the human microbiome. The $150 million initiative, begun in 2007 by the NIH, has followed hundreds of healthy people and sequenced genetic material from their bodily bacteria -- a harvest of more than 5 million genes [sources: HMP; Zimmer; Zimmer].

The HMP currently funds 15 projects with potential to show correlations between the microbiome and human health and diseases such as psoriasis, Crohn's disease, ulcerative colitis and esophageal cancer, among others [sources: Borody; HMP; Stein].

One Man's Trash ...

We stand on the threshold of a microbiotic renaissance, according to some physicians and microbiologists. As our understanding of this long-neglected field expands, so too will our treatment options.

As we mentioned, the place to start -- at least where fecal transplantation is concerned -- remains Clostridium difficile. According to the CDC, C. difficile infections kill 14,000 people in the United States annually, and its occurrence among hospitalized patients more than doubled from 2000 to 2009 [sources: Hudson; Zimmer]. One long-term follow-up study of 77 fecal transplant patients reported a 91 percent cure rate after just one fecal transplant, and a 98 percent cure rate with additional probiotics, antibiotics or fecal transplants [source: Brandt et al.].

Fecal microbiota might also hold answers for people with metabolic syndrome -- a collection of co-occurring risk factors, such as insulin resistance and extra weight around the middle, that increases the chance of coronary artery disease, stroke and type 2 diabetes [source: A.D.A.M.]. In some studies, fecal transplantation in metabolic syndrome patients reduced triglyceride levels and improved insulin sensitivity [source: Allen; Gewirtz].

Scientists have also tied obesity in rats to changes to the gut's microbiome. The intestines of obese persons contain a different set of microbes than those of non-obese persons, and clinical trial results suggest lean donors might help obese recipients lose weight by changing how they metabolize sugars [source: Zimmer].

"The composition and activity of gut microbiota is different in lean and obese individuals," says Dr. Alexander Khoruts, associate professor of medicine at University of Minnesota. "We know that animal energy metabolism can be changed by fecal microbiota transplantation. It is possible there will be something along these lines in humans."

"However, it is also clear that diet and lifestyle choices influence the composition of gut microbiota."

Indeed, we're only beginning to grasp the possibilities for fecal transplants and macrobiotics in general [source: Khoruts]. Don't confuse the two, however. Gut flora, though numerous, represent only a portion of total body microbes. Moreover, we do not yet fully understand the relationships between microbiota, health and disease, whether in the intestines or outside of them.

For example, a number of medical conditions may be linked to the intestine, including liver disease, migraines, chronic fatigue, rheumatoid arthritis, multiple sclerosis, Alzheimer's disease and Parkinson's disease, but how (or if) they relate to microbial therapy or fecal transplants remains unclear and will require substantial studies to answer [sources: Allen; Borody; Borody; Khoruts].

In the meantime, don't be too quick to "poo-poo" the idea of fecal transplantation. It's effective, fast and seems to have no side effects. But, as with any new therapy, we'll have to wait and see how it comes all out in the end.

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Authors Note: How Fecal Transplants Work

No matter how long I report on science, it never ceases to surprise. Perhaps there is nothing new under the sun, but what about where the sun doesn't shine?

Vulgarities and terrible puns aside, few things are as fun for a science journalist as when scientists or doctors point to something we take for granted and say, "Hmm, maybe this is more important than we thought," or, "Perhaps our assumptions are completely out of whack and we need a paradigm that's less than a century old."

Such cycles are a natural part of science. Research, after all, runs hot and cold, and yesterday's apparent dead-end can later open up into today's road to discovery. All it takes is a pair of fresh eyes and the context provided by time and further research.